"We were sometimes called disease detectives," Henderson recalls, "and were on-call 24-hours-a-day to go anywhere in case of an epidemic."

Henderson left the CDC after his required service, only to return in 1960 with a degree in public health. Appointed to head a surveillance unit, he was asked to work on a project run by the U.S. Agency for International Development to fight measles in West Africa. He felt the effort was doomed to fail unless it had adequate funding for yearly vaccinations.

Instead, Henderson proposed adding smallpox to the USAID measles program, a plan he never expected would win approval, least of all from the U.S. president.

"Suddenly, we were running a program for 20 countries in West Africa [for] more than 100 million people and trying to put together a staff, transport and vaccine," Henderson says.

In the end, Henderson and his colleagues were able launch a combined measles-smallpox program. The following year, the World Health Organization would back a global plan to eradicate smallpox. Henderson was chosen to lead the international effort in countries where smallpox was endemic. He managed large campaigns in South America, sub-Saharan Africa and Asia with a scant $2.5 million budget.

From the start, Henderson felt eradication was possible. There was an effective single-dose, low-cost vaccine and injector guns and newly designed needles that could deliver vaccine rapidly. Most importantly, rather than vaccinate everyone in every country, Henderson says his vaccination strategy would be based on case reporting and containment.

"You go to the place where the cases are, see if there are other cases around," he says. "You vaccinate them, and you build a kind of wall around them of [vaccinated] people because smallpox will not exist in animals. It has to go from people to people to people, and if you break that chain at any point, smallpox stops."

Henderson had a small international staff, and so he relied on local health workers, an effort often complicated by floods, nomadic populations, kidnappings and armed conflict.

"We had the civil war problem in several countries. Ethiopia was particularly difficult, where the emperor was assassinated, and there was a Marxist coupe where they took over. And there was a long period there where the only people allowed out of the capital were those working in the smallpox program."

Henderson also cultivated cooperation with the Soviet Union during the Cold War. As a result, Moscow not only contributed massive amounts of vaccine, but it also afforded Henderson a diplomatic channel to countries hostile to the United States.

"Somalia was one of the countries hiding cases, and we got our reports from the Russian embassy," he says.

The eradication strategy was put to its biggest test in 1977 in India, then a country of 700 million people, where Henderson ordered mobilization on a grand scale.

"After the third [country-wide] search [for cases], it got better organized, and we soon found that we could go to 90 percent of the houses in India in 10 days."

Victory in India meant the end was near, Henderson recalls. In 1980, the World Health Organization declared the world smallpox-free. By then, Henderson had moved on to head the Johns Hopkins School of Public Health in Baltimore, Maryland. He also has served off-and-on as a top government science advisor.

The possibility that smallpox could re-emerge as a biological weapon was not thinkable during the eradication effort, but in its aftermath was the impetus that led Henderson to create the Center for Biosecurity in Baltimore, Maryland. The center engages a community of doctors, health officials and researchers in planning for a potential future disease outbreak.

"My concern was to try to get us prepared in case there was a rogue agent of some sort to distribute [a] virus that we were prepared to cope with it," he says.

"It's been very rewarding," he says, "And you feel good at the end of a day when you know that you have changed the world in a lot of different ways with a lot of other people working with you in doing it. It's not a one-man show."